DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant's election with traverse of Group I (Claims 1-9 and 22) and the following species:
SEQ ID NO: 6 for the protein encoded by the rVSV;
SEQ ID NO: 2 as the polynucleotide sequence encoding for SEQ ID NO: 6; and
Applicant has cancelled the claims requiring the election for the promoter
in the reply filed on 28 July 2026 is acknowledged. The traversal is on the ground that searching the additional species will not cause unduly burden. This is not found persuasive because Applicant is applying a different standard to traverse the restriction requirement. Search burden is irrelevant to National Stage (371) applications.
The requirement is still deemed proper and is therefore made FINAL.
Claims 10-14 and 16-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 28 July 2026.
Claim Status
3. Claims 5 and 15 are cancelled.
Claims 10-14 and 16-21 are withdrawn.
Claims 1-4, 6-9, and 22 are under consideration.
Priority
4. The Instant Application is a National Stage (371) of PCT/US2022/076850 filed 22 September 2022, which claims priority to U.S. Provisional Application No. 63/248,055 filed 24 September 2021. Claims 1-4, 6-9, and 22 of the Instant Application are supported by U.S. Provisional Application No. 63/248,055 and thus the U.S. effective filing date of the Instant Application is 24 September 2021.
Information Disclosure Statement
5. The information disclosure statement (IDS) submitted on 19 March 2024 was filed before the mailing date of the Non-Final Office Action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
NPL titled "Recombinant Measles Virus Vaccine Expressing the Nipah Virus Glycoprotein Protects against Lethal Nipah Virus Challenge" by Yoneda et al. was attached but not cited on the IDS. Thus, this reference is not being considered by the Examiner.
6. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
7. The drawings are objected to because:
The lines in FIGs. 2A-B, 10A-B, 11A-D, 13A-C, 14A-C cannot be distinguished;
The triangles in FIGs. 5A and 5B cannot be distinguished;
The key for FIGs. 13A-C appears to be next to FIG. 13D;
The different sections of the pie chart and the keys/tables underneath cannot be distinguished in FIG. 14D;
FIGs. 15A-D are indistinguishable; what is presumably FIG. 15C is not on the correct page; and
The description for FIGs. 1B, 2A-B, 5A-B, 6, 7A-D, 8A-B, 9, 10A-B, 11A-D, 12A-12T, 13A-D, 14A-D, 15A-F refer to color (See ¶ [0014]-[0015], [0018]-[0027], [0029]).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Nucleotide and/or Amino Acid Sequence Disclosures
8. Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
9. Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
See ¶ [0155].
Specification
10. Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because it recites “The present invention”. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
11. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http://, www., or other browser-executable code. See MPEP § 608.01.
See ¶ [0202], [0205], [0227], [0253]. Note that these are merely examples and all hyperlinks and/or other form of browser-executable code should be identified by Applicant and properly addressed.
Claim Objections
12. Claims 1-3, 6-7, and 22 objected to because of the following informalities:
Regarding claim 1, the first instance of “NiVB” in line 4 should be defined instead of the final instance.
Regarding claim 1, “…G-protein antigen comprises an amino acid…” in line 4 should read “…G-protein is an antigen that comprises an amino acid…” for clarity. The same instance in claim 22, lines 4-5 should be addressed accordingly.
Regarding claims 1 and 22, “wherein the heterologous polynucleotide has” should be inserted before “90% sequence identity to a nucleic acid sequence as set forth in SEQ ID NO: 2” in line 7.
Regarding claims 2-3 and 6, “heterologous” should be inserted before “polynucleotide” in line 1 for clarity.
Regarding claim 7, there should be a comma after “vehicle” for clarity.
Appropriate correction is required.
13. Applicant is advised that should claim 1 be found allowable, claim 22 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112(b)
14. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
15. Claims 1-4, 6-9, and 22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 1 and 22, the recitation of “an amino acid sequence as set forth in SEQ ID NO: 6” and “a nucleic acid sequence as set forth in SEQ ID NO: 2” is unclear because it could be interpreted as requiring the whole sequence or a fragment thereof. Thus, there are multiple structural interpretations.
Claims 2-4 and 6-9, which depend on claim 1, are similarly rejected.
Regarding claims 1 and 22, “comprising a recombinant vesicular stomatitis virus (rVSV) viral vector that expresses a Nipah Virus protein” is unclear because the vector itself need not necessarily express the protein on its surface but it could. The presence of multiple structural interpretations renders the claims indefinite.
Claims 2-4 and 6-9, which depend on claim 1, are similarly rejected. Applicant may consider using encodes rather than expresses if this is the desired scope.
Regarding claims 2-4 and 6-9, the recitation of “composition or vaccine” in line 1 makes it unclear if the composition, vaccine, or both are being further limited. Thus, the BRI of each claim is indefinite. It is suggested that all presented claims under examination be drawn to compositions only. Applicant may consider adding a vaccine claim that depends on claim 1, for example, and further adds an adjuvant.
Regarding claim 3, the claim recites “the polynucleotide” but the sequence recited (SEQ ID NO: 6) is an amino acid sequence. Examiner is interpreting this claim to be that the polynucleotide encodes SEQ ID NO: 6 but the claim is structurally indefinite without a reference sequence of proper biomolecule type.
Regarding claim 7, it is unclear if “pharmaceutically or veterinary acceptable” applies to just the carrier, or to every item in the list. A composition is not necessarily pharmaceutical. The presence of multiple interpretations renders the claim indefinite.
See Ex parte Miyazaki, 89 USPQ2d 1207 (BPAI 2008) ("[R]ather than requiring that the claims are insolubly ambiguous, we hold that if a claim is amenable to two or more plausible claim constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. §112, second paragraph, as indefinite.").
Claim Rejections - 35 USC § 112(d)
16. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
17. Claim 8 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Due to the presence of the “or” language, in one embodiment, claim 8 requires that the composition or vaccine of claim 1 does not comprise a gene. Claim 1 requires a gene, and thus not every embodiment of claim 8 has all limitations of claim 1 from which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form so long as no duplicates are made, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(a) – Written Description
18. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
19. Claims 1-4, 6-9, and 22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims above are drawn to a polynucleotide that has at least 90% identity to SEQ ID NO: 2 and/or encodes a NiVB G-protein that has at least 90% identity to SEQ ID NO: 6. This reads on any and all possible mutations and truncations that keep at least 90% of the sequences intact. Thus, it is clear that the breadth of the recited polynucleotides and encoded peptides in the claims far overreaches Applicant’s contribution as disclosed in the specification and so this rejection is made. One of ordinary skill in this art cannot conclude that Applicant was in possession of any and all possible mutations of SEQ ID NOs: 2 and 6. An enormous breadth of possible polynucleotides and encoded peptides are thus not represented by Applicant at all. Even if the prior art is aware of other mutated polynucleotides and their respective encoded peptides, the totality of known mutations would not be representative of the entire genus for the reasons discussed below.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
An applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 111 USPQ2d 1780 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, as here in which the peptide inhibitors can have any sequence, one must describe a sufficient variety of species to reflect the variation within the genus. However, one of skill in this art cannot envision the structure of any other peptides with the required function other than the few species provided by Applicant and the prior art. Therefore, since only a few species are provided to represent the genus, the claims encompassing the same clearly fail the written description requirement.
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. See ABBVIE DEUTSCHLAND GMBH & 2 CO. v. JANSSEN BIOTECH, INC., Appeals from the United States District Court for the District of Massachusetts in Nos. 09-CV-11340-FDS, 10-CV-40003-FDS, and 10-CV-40004-FDS, Judge F. Dennis Saylor, IV. See also Ariad, 598 F.3d at 1351 (“[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”).
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members.
“Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species.” Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010). Since there are only a few presented polynucleotides and encoded peptides taught by Applicant, and mutated polynucleotides/peptides would vary in structure, there is no correlation between structure and function between the members of the recited or any genus. Additional mutated polynucleotides could read on any and all combinations of base pairs, as well as encoded amino acids. Thus, since there is no correlation between structure and peptide function across the entire genus, functional language should not be used to define a genus. Rather, structure should be used, including the core sequence required for said function.
Even when several species are disclosed, these are not necessarily representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. Since the genus recited in the instant claims is large, it would be very challenging to describe sufficient species to cover the structures of the entire genus.
Overall, at the time the invention was made, the level of skill for preparing peptides and then selecting those peptides with desired functional properties was high. However, even if a selection procedure was, at the time of the invention, sufficient to enable the skilled artisan to identify peptides with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010). Absent the conserved structure provided by a core inhibitory peptide sequence, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what any peptide with a particular set of functional properties would look like structurally.
Since no mutations are taught in the specification of the recited genus above, the instant claims above clearly fail the written description requirement. A representative number of species has not been taught to describe such a massive genus. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe said genus.
Owed to the variation among the peptides of the genus as broadly as currently claimed, it is very difficult to provide adequate representation of the functionally defined peptide genus. There is unlikely to be any structure (subsequence) shared by the entire genus. If there is a subsequence common to all or some of Applicant’s species, then the claims should recite that as part of the peptide genus to provide adequate representation of the actual disclosed/possessed group. Also, the disclosure of one group of highly related peptides does not guide one of skill to the next peptide of the genus with said function. Finding another said peptide would require mutation and it is well-known in this art that mutation of peptides leads to specific function loss.
The art teaches that protein chemistry is probably one of the most unpredictable areas of biotechnology. For example, replacement of a single “lysine” residue at position 118 of acidic fibroblast growth factor by “glutamic acid” led to the substantial loss of heparin binding, receptor binding and biological activity of the protein (Burgess, 1990, J. Cell Bio., 111: 2129-2138). In transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen (Lazar, 1988, Molecular and Cellular Biology, 8: 1247-1252). As these references illustrate, it is unpredictable that a polypeptide variant of a known target protein binder will also bind said target. It is also unpredictable that they would bind said target in the same way, having the same effect on the target (i.e. inhibit or activate). Ju (1991, PNAS, 88: 2658-2662) teaches that the interleukin 1 receptor (IL-1R) antagonist IL-1ra is a naturally occurring protein with no agonist activity in vitro or in vivo (Abstract). However, substitution of a single amino acid lysine145 to aspartic acid changes the property of this peptide to a partial agonist of IL-1R (Abstract). Thus, even a single substitution can change the biological property of a peptide.
This substitution need not be at a position where said residue would contact the target protein. Baker (2000, Immunity, 13: 475-484) teaches that Tax-peptide is an agonist of the of T cell activity (Abstract). However, mutation of proline at position 6 of this peptide to alanine creates a T cell antagonist (Abstract). Importantly, this residue does not contact the T cell receptor (Abstract).
In summary, these examples teach that the biological function of peptide variants is unpredictable because even a single mutation can abolish activity or give a different function. For example, agonist and antagonist peptides can be interconverted through mutagenesis. Importantly, binding can still occur after mutation, illustrating that a simple show of binding is not predictive of the nature of a peptide’s biological activity. This point is underlined by Montrose-Rafizadeh (1997, J. Biol. Chem., 272: 21201-21206) who teaches that receptor binding does not predict agonist or antagonist activity (Pg. 21205, Column 2, Paragraph, first full, Sentence, first).
Thus, while applicant has described a few species within the genus recited, and the art may provide more, each genus is very large and would encompass peptide structures that cannot be visualized from the prior art or instant disclosure. One of skill in this art cannot determine the peptide structures encompassed by the claimed/recited genus only defined by function. Any future peptide may or may not be encompassed, and if it is, it would not have been represented in Applicant’s disclosed species. Thus, the described species cannot be considered representative of the entire recited genus of peptides. E.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, the claims are rejected here.
As discussed above, an applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613. Therefore, it is recommended that the instant claims be amended to recite that the peptide genus must comprise the core peptide responsible for the recited function as this would define the structure/function relationship of the species Applicant possesses.
Claim Rejections - 35 USC § 112(a) – Enablement
20. In making a determination as to whether an application has met the requirements forenablement under 35 U.S.C. 112 ¶ 1, the courts have put forth a series of factors. See, In reWands, 8 USPQ2d 1400, at 1404 (CAFC 1988). The factors considered include: (1) the breadth of the claims, (2) the nature of the invention, (3) the relative skill of those in the art, (4) the presence or absence of working examples, (5) the amount of direction or guidance provided, (6) the state of the prior art, (7) the level of predictability in the art, and (8) the quantity of experimentation necessary.
21. Claims 1-4, 6-9, and 22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a defined protein shown to function and polynucleotide encoding the same, does not reasonably provide enablement for any and all possible mutations of the polynucleotide and subsequently encoded peptide. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
The claims are drawn to a composition or vaccine comprising an rVSV vector with a polynucleotide encoding a NiVB G-protein.
The nature of the invention is a vaccine against Nipah Virus.
The level of skill of one of ordinary skill in this art is high.
The specification provides working examples wherein the rVSV-ΔG-NiVB G construct is tested, which has a SEQ ID NO: 2 (Examples 1 and 2). ¶ [0135] shows that neutralizing antibodies were made in response to this vaccine.
The art teaches that protein chemistry is probably one of the most unpredictable areas of biotechnology. For example, conservative replacement of a single “lysine” residue at position 118 of acidic fibroblast growth factor by “glutamic acid” led to the substantial loss of heparin binding, receptor binding and biological activity of the protein (Burgess, 1990, J. Cell Bio., 111: 2129-2138). In transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen (Lazar, 1988, Mol. Cell. Biol., 8: 1247-1252). As these references illustrate, it is unpredictable that a polypeptide variant of a known target protein binder will also bind said target. It is also unpredictable that they would bind said target in the same way, having the same effect on the target (i.e. inhibit or activate). Ju (1991, PNAS, 88: 2658-2662) teaches that the interleukin 1 receptor (IL-1R) antagonist IL-1ra is a naturally occurring protein with no agonist activity in vitro or in vivo (Abstract). However, substitution of a single amino acid lysine145 to aspartic acid changes the property of this peptide to a partial agonist of IL-1R (Abstract). Thus, even a single substitution can change the biological property of a peptide.
This substitution need not be at a position where said residue would contact the target protein. Baker (2000, Immunity, 13: 475-484) teaches that Tax-peptide is an agonist of the of T cell activity (Abstract). However, mutation of proline at position 6 of this peptide to alanine creates a T cell antagonist (Abstract). Importantly, this residue does not contact the T cell receptor (Abstract).
In another case, Huang (1997, J. Biol. Chem., 272(43): 27155-27159) teaches that conjugation of peptides to other proteins can change their biological properties. They teach that multiple conjugation of the peptide TGFβ1 (residues 41-65) to carrier proteins enhances its antagonist activity but also confers partial agonist activity as well (Abstract). Thus, the chemical context of a biologically active peptide is also important.
Truncation of proteins can also lead to adverse effects on protein structure and thus protein function. Martindale (1998, Nat. Genet., 18: 150-154) teaches that truncation of huntingtin leads to aggregate development which compromises cell viability (Abstract). Nonaka (2009, Hum. Mol. Genet., 18(18): 3353-3364) teaches that truncation of TDP-43 to its C-terminal fragments causes abnormally phosphorylated and ubiquitinated inclusions of the protein (Abstract). Taken together, not just any truncation of a protein will yield a soluble, functional, protein fragment.
In summary, these examples teach that the biological function of peptide variants is unpredictable because even a single mutation can abolish activity or give a different function. For example, agonist and antagonist peptides can be interconverted through conjugation or mutagenesis. Importantly, binding can still occur after mutation or conjugation in the literature examples provided above, illustrating that a simple show of binding is not predictive of the nature of a peptide’s biological activity. This point is underlined by Montrose-Rafizadeh (1997, J. Biol. Chem., 272: 21201-21206) who teaches that receptor binding does not predict agonist or antagonist activity (Page 21205, Column 2, ¶ first full, first sentence).
With respect to the use of peptides in the treatment of a disease such as cancer, the state of the art at the time of filing was such that it was unpredictable whether or not a peptide would function therapeutically. Their functionality depends, in part, on whether or not they reach their intended target in a sufficient quantity as to cause a therapeutic effect. Mendoza (2005, Arch. Immunol. Ther. Exp., 53: 47-60) teaches that peptides derived from larger molecules that are important modulators of apoptosis are frequently becoming leads for the development of anticancer therapeutics (Page 48, Column 2, ¶ first partial). However, they also state that natural peptides have low bioavailability and short half-life in the mammalian circulation system, while synthetic peptides have potential cytotoxicities (Page 57, Column 1, ¶ last full). Due to these characteristics, systematic testing in in vivo as well as in vitro settings must be done rigorously to verify peptide applications in the clinic (Page 57, Column 1, ¶ last full). Taken together, barring experimental evidence, no peptide can merely be assumed to function in the treatment of a disease, for example cancer, in vivo just because it functions as an inhibitor in vitro.
Since the art teaches that it is unpredictable whether or not peptide variants of known inhibitors will function as such and it is also unpredictable that even a known inhibitory peptide that functions in vitro will function in vivo, it would also be unpredictable to that the polypeptide variants will retain their original function or function as desired. Since the specification does nothing to ameliorate these concerns, one would be burdened with undue experimentation to use the products of instant claims as broadly as they are currently claimed.
Claim Rejections - 35 USC § 103
22. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
23. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
24. Claims 1-4, 6-9, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Jansy (US 20190351047 A1; Published 21 November 2019) (See IDS filed 19 March 2024) in view of Van den Pol (28 February 2017, J. Virol., 91(6)) and Odani (US 20090155277 A1; Published 18 June 2009).
Regarding claims 1, 3-4, 6, 8-9, and 22, Jansy teaches “In particular, the present invention concerns a Hendra virus and/or Nipah virus vaccine. The present invention is directed to an artificial nucleic acid, polypeptides, compositions and vaccines comprising the artificial nucleic acid or the polypeptides.” (Abstract), a vector suitable for incorporating or harboring a desired nucleic acid sequence (¶ [0080]), and an antigen that can be the Nipah Virus amino acid sequence of SEQ ID NO: 13 (¶ [0061]). SEQ ID NO: 13 is a Nipah Virus G-protein that has a 100% match to SEQ ID NO: 6 of the Instant Application:
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The alignment has been omitted due to its length. Jansy does not teach rVSV as the viral vector or where the G-protein is inserted.
However, Van den Pol teaches "VSVs that include the VSV glycoprotein (G) gene, even in most recombinant attenuated strains, can still show substantial adverse or lethal actions in the brain. Here, we test 4 chimeric viruses in the brain, including those in which glycoprotein genes from Nipah, chikungunya (CHIKV), and influenza H5N1 viruses were substituted for the VSV glycoprotein gene." (Abstract) and Figure 1:
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Wherein the bottom construct is a VSV with its G protein deleted and has the Nipah Virus G protein inserted between the VSV M and L proteins (Figure 1 caption). Therefore, it would have been obvious to one of ordinary skill before the filing date to take a nucleic acid sequence encoding the Nipah G-protein (SEQ ID NO: 13) of Jansy and insert it into the VSV vector taught by Van dan Pol, which has no Green Fluorescent Protein. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02). Furthermore, this obvious vector is encompassed within the taught genus of Jansy and so carries a reasonable expectation of success. It lacks the VSV G protein gene and so will avoid the side effects taught by Van den Pol and so carry this obvious advantage, which would have been recognized by a PHOSITA. Also, it is clear that VSV are desirable vectors as Van den Pol seeks to improve them for pharmaceutical use to include as vaccines (Abstract).
This vaccine will inherently be effective to reduce or prevent a Nipah Virus at 3 days, elicit an immune response within 3 days, and provide protection at 7 days against both the Malaysia and Bangladesh strains as it is materially identical to the claimed invention and thus must have the same properties. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). “When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). “Products of identical chemical composition can not have mutually exclusive properties.” A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990)
Regarding claim 2, Jansy teaches the amino acid sequence SEQ ID NO: 13, which encodes a Nipah Virus G-protein, but does not teach the specific nucleic acid sequence. However, Odani teaches
all codons for each amino acid (¶ [0112]) and so all nucleic acids that encode one protein sequence are obvious. According to the genetic code, each amino acid in a protein can be encoded by one of a small number of possible triplet codons in a nucleic acid. That is, those skilled in the art are aware that only a limited number of codons can encode a specific amino acid, and that the genetic code provides a known correlation between the codon function (encoding a specific amino acid) and each codon structure. The use of any known codon for the desired amino acid is merely use of one known codon to arrive at predictable results, which is the generation of the desired protein domains. Thus, one skilled in the art would be able to readily envision all the nucleotide sequences capable of encoding the amino acid sequence of SEQ ID NO: 6, which would include SEQ ID NO: 2.
Regarding claim 7, Jansy further teaches “In another aspect, the invention relates to a composition comprising at least one artificial nucleic acid as described herein and at least one pharmaceutically acceptable carrier.” (¶ [0098]) and “The composition may further comprise at least one adjuvant component.” (¶ [0105]). These are obvious to add to the obvious vector above and would have been to a PHOSITA before the filing of the instant case because of Jansy’s teachings and the fact that it was standard practice in the vaccine arts.
Conclusion
25. No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTINA E LY whose telephone number is (571)272-5169. The examiner can normally be reached Monday - Thursday, 8:00 am - 5:00 pm EST.
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/KRISTINA E. LY/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671
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